Outline

Expression of the proto-oncogene c-kit, a marker which characterizes the hematopoietic stem cell, has been found in malignant tissue including a subset of breast cancers. c-Kit is also expressed in normal breast tissue and several authors found a loss of c-kit expression in breast carcinoma suggesting it might be involved in the growth control of mammary epithelium. Until now, only a few markers were described to be co-regulated with c-kit as e.g. CK-5/-17, Her-1 and PDGFR. To elucidate the possible role of c-kit in malignant transformation, we analyzed gene expression data of breast cancer patients.

Summary: A total of 10.5 % of the tumors showed strong c-kit expression (2.5 fold above median). Simple comparison of gene expression profiles of 10 samples with highest c-kit vs. those 10 with lowest expression did not reveal genes with a good correlation to c-kit. However, when samples were first subdivided into molecular tumor subtypes using the intrinsic gene set according to Sorlie et al., and different tumor subtypes were analyzed separately, a strong correlation of c-kit expression with a large cluster of genes containing several for whom c-kit coexpression was already described (HER1, CK-5/-17, PDGFR) as well as several members of the wnt signalling pathway could be revealed, providing a possible novel link to mammary epithelial differentiation and a putative role in characterizing mammary stem cells. Furthermore we could observe within this cluster two distinct subgroups characterized by different ER-expression and high or low proliferation rate.

Conclusions: Gene expression analysis of mammary tumor subgroups according to Sorlie et al. provides new insight in the biological function of c-kit. In combination with wnt-associated genes and differences in ER-expression and high or low proliferation rate, two subgroups with stem-cell-like features can be distinguished, suggesting the existence of a two-stem-cell-hypothesis according to Dontu et al., (Endocrinol Metab, 15(5):193-7, 2004).